The long-term objective of this research plan is to understand the molecular events at the protein level of cellular changes that drive the evolution of neoplastic disease. The focus is on the development and implementation of laser capture micro-dissection and mass spectrometry technologies for the screening of prostate and ovarian cancer and/or tissue-specific protein markers for early diagnosis, risk assessment, and 2anticancer drug evaluation. The methodology involves the isolation of cancer cells from human tissues by laser capture micro-dissection, protein separation by high-resolution 2D-gel electrophoresis, and identification of target proteins by mass spectrometry. The specific aims of this research: 1. To use a combination of modern techniques to analyze proteins and protein profiles directly from premalignant and malignant subpopulations of cells selected under microscopic visualization of actual cancer tissue specimens. 2. To define the protein changes that occur in prostate and ovary cancer progression which correlate with disease stage and arise at the earliest premalignancies. 3. To identify specific proteins and protein profiles from patient sample study sets for further analysis in patient-matched body fluid for marker identification. The initial utility of these studies will be to aid clinicians in early diagnosing prostate and ovarian cancer patients at an early stage of the diseases. These studies will also provide means to accurately predict prognosis and help clinicians recommend the most appropriate treatment and follow up strategies for their patients. Thus, this research will contribute to prolonging survival and reducing mortality of prostate and ovarian cancer patients.